ABSTRACT
Inhibitors of Angiogenesis-Endostatin and Endostatin-Like Fragment from Type XV Collagen (EFC-XV) ............................................. 195
14.5 Perlecan-Derived Endogenous Inhibitor of Angiogenesis-Endorepellin ... 196 References .............................................................................................................. 197
The extracellular matrix (ECM) is a complex structure composed of proteins, proteo glycans, and adhesive glycoproteins that provides structural and mechanical support to cells and tissues, as well as regulates a wide variety of cellular processes. The effects of ECM are mainly mediated by cell surface integrins (Giancotti and Ruoslahti 1999; Hynes 1992). At the structural level, there are two major forms of ECM: the interstitial matrix and the basement membrane (BM). While the interstitial matrix is a fibrillar network that allows cell movements through the tissues, the BM is a dense, sheet-like structure serving as a barrier to keep cells of various types separated from the surrounding stroma. The predominant components of the BM include type IV collagen, laminin, heparan-sulfate proteoglycans (HSPGs), and nidogen/entactin. Smaller amounts of type XV collagen, type XVIII collagen, fibulins, osteopontin/SPARC/BM-40, and agrin are also found in the BM. Via the
self-assembly laminin and type IV collagen, BMs form super-molecular networks providing a scaffold with which nidogen, HSPG, and other BM proteins interact and adhere. The specific protein components of the BM vary from tissue to tissue , thus contributing to the tissue-specific morphology and function. The vascular basement membrane (VBM), sandwiched between blood vessel endothelial cells and mural cells (vascular smooth muscle cells and pericytes), is important for providing structural support and also regulation of angiogenesis-the formation of new blood capillaries from pre-existing vasculature (Kalluri 2003).
